Antiproliferative effect of phenylethanoid glycosides from Verbena officinalis L. on Colon Cancer Cell Lines

•Bioassay guided fractionation led to the isolation of 12 phenylethanoid glycosides with anti-proliferative activity.•Aqueous extract of V. officinalis showed antiproliferative activity on two Colon Cancer Cell Lines.•Five new acetyl-phenylethanoids have been isolated.•Compounds exhibiting vicinal acetyl-groups in the sugar rings were particularly strong cytotoxic compounds.

The cytotoxic effect of the aqueous extract from Verbena officinalis, was evaluated in vitro on DHD/K12/PROb rat colonic epithelial cell line and HCT-116 human colon adenocarcinoma cell line. In both cell lines, the IC50 values were lower than 20 μg/mL after 72 h of treatment. Bioassay guided fractionation led to the isolation of 12 phenylethanoid glycosides with anti-proliferative activity, five of them are being reported for the first time. The new compounds were elucidated as 4‴-acetyl-O-isoverbascoside, 2″,4″-diacetyl-O-verbascoside, 3‴,4‴-diacetyl-O-isoverbascoside, 4‴,6″-diacetyl-O-betonyoside A and 3‴,4‴-diacetyl-O-betonyoside A. The IC50 results suggest that antiproliferative activity is determined by not only the number of acetyl-groups but also their position in the aliphatic rings. Compounds exhibiting vicinal acetyl-groups in the sugar rings such as 3‴,4‴-diacetyl-O-isoverbascoside and 3‴,4‴-diacetyl-O-betonyoside A are particularly strong cytotoxic compounds against both cell lines. This investigation indicated that diacetyl-phenylethanoids might be valuable as cancer chemopreventive agents.